期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 58, 期 8, 页码 2326-2330出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201812623
关键词
biosynthesis; double bonds; enzymes; fatty acids; polyketides
资金
- MEXT, Japan (JSPS KAKENHI) [16H06452]
- JSPS [15H03110, 18H03937]
- Grants-in-Aid for Scientific Research [18H03937, 16H06452, 15H03110] Funding Source: KAKEN
Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) are essential fatty acids for humans. Some microorganisms biosynthesize these PUFAs through PUFA synthases composed of four subunits with multiple catalytic domains. These PUFA synthases each create a specific PUFA without undesirable byproducts, even though the multiple catalytic domains in each large subunit are very similar. However, the detailed biosynthetic pathways and mechanisms for controlling final-product profiles are still obscure. In this study, the FabA-type dehydratase domain (DHFabA) in the C-subunit and the polyketide synthase-type dehydratase domain (DHPKS) in the B-subunit of ARA synthase were revealed to be essential for ARA biosynthesis by in vivo gene exchange assays. Furthermore, in vitro analysis with truncated recombinant enzymes and C-4- to C-8-acyl ACP substrates showed that ARA and EPA synthases utilized two types of DH domains, DHPKS and DHFabA, depending on the carbon-chain length, to introduce either saturation or cis double bonds to growing acyl chains.
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